Sodium Carbonate → {2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester

HRID 1072587

Reaction equation

HRID 1072587 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[C:34]([O:38][C:39]([NH:41][C:42]([CH3:62])([CH3:61])[CH2:43][C:44]1[C:52]2[C:47](=[C:48](OS(C(F)(F)F)(=O)=O)[CH:49]=[CH:50][CH:51]=2)[NH:46][CH:45]=1)=[O:40])([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.[Cl-].[Na+].O.C(OCC)(=O)C>[C:34]([O:38][C:39](=[O:40])[NH:41][C:42]([CH3:62])([CH3:61])[CH2:43][C:44]1[C:52]2[C:47](=[C:48]([C:2]3[CH:10]=[CH:9][C:5]([C:6](=[O:7])[NH2:8])=[CH:4][CH:3]=3)[CH:49]=[CH:50][CH:51]=2)[NH:46][CH:45]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 696834-BromobenzamideHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86595245trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

Product 1

HCID 69517685{2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl esterYield 58.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 4-bromobenzamide (150 mg, 0.75 mmol), bis(pinacolato)diboron (209 mg, 0.825 mmol), potassium acetate (0.221 g, 2.25 mmol) and {1,1′-bis(diphenylphosphino)-ferrocene}dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) in dimethylsulfoxide (5 mL) is heated to 80° C. for two hours. The mixture is cooled to 20° C. and trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (262 mg, 0.600 mmol), {1,1′-bis(diphenylphosphino)-ferrocene}dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) and sodium carbonate (1.9 mL, 2M, 3.75 mmol) are added. The mixture is heated to 80° C. overnight. The mixture is diluted with brine and ethyl acetate. The organic fraction is washed seven times with brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The residue is purified using silica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution) to give 143 mg of {2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester (58%). FDMS m/e=408 (M++1).

Workup

  1. temperatureThe mixture is heated to 80° C. overnight
  2. washThe organic fraction is washed seven times with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue is purified
  7. washsilica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-b117ec0320594f8ea6ffa2a0faa439b5
Source dataset
uspto-grants-2005_06
Patent number
US06911463B2

Linked notes

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